The present invention relates to high calorie solutions for intravenous administration to human patients and methods of administering such solutions. More particularly, the present invention relates to solutions comprising glucose polymer mixtures of low molecular weight which can be infused into and utilized by human patients in relatively high concentrations without requiring use of a central vein. The present invention further relates to methods of preparing the high calorie solutions and preferred rates of their infusion. Still further, the invention relates to the utilization of the solutions by diabetic human patients.
Major nutritional problems are seen in many human patients who for one reason or another cannot obtain an adequate supply of calories by mouth. The problems are particularly acute in unconscious patients, surgical patients who have lost a large amount of weight preoperatively, and in patients in protracted convalescence for such diseases as bowel obstruction, peritonitis, or intestinal fistulae.
Because the patient requires energy to maintain life and must constantly synthesize protein tissue, it is essential that the patient's caloric and protein intake be maintained at least at minimum levels. In the absence of any exogenous source of nutrition, the patient will obtain needed calories by catabolism of endogenous fat stores and protein tissues. This can lead to death by starvation, lack of resistance to infection, respiratory muscle failure, or cardiac muscle failure. Accordingly, the intravenous administration of nutrients to the patient can be life-saving.
Conventionally, aqueous solutions of glucose or fructose have been infused into patients intravenously to provide exogenous calories. Because of the osmotic relationship between human plasma and blood corpuscles, an important consideration of any solution parenterally administered to a patient is that it can cause damage to the patient's corpuscles if it is not substantially isotonic to human blood. If the patient's plasma becomes strongly hypertonic, the corpuscles shrivel. If it becomes strongly hypotonic, the corpuscles swell and may burst. Accordingly, the aqueous solutions of glucose or fructose most commonly intravenously infused into a patient are such isotonic 5% W/V solutions.
One liter of 5% W/V glucose solution provides 50 grams of glucose per each 1000 ml. of solution. Each gram of glucose provides 3.4 calories and, therefore, one liter of a 5% W/V glucose solution provides 170 calories per each 1000 ml. of solution. Generally, adult patients require a total of 2,000-5,000 calories per day. To satisfy that need, a patient would have to receive from 12-35 liters of 5% W/V glucose solution per day. Clearly, such an infusion of 12-35,000 ml. of water would grossly over-hydrate the patient.
Alternatively, hypertonic glucose or fructose 10 to 20% W/V solutions can and have been intravenously injected in order to provide the patient more calories. However, their infusion for extended periods of time is limited by the inability of the patient's peripheral veins to handle such hypertonic solutions without serious venous thrombosis or thrombophlebitis resulting.
It is well known that 25-50% W/V solutions of glucose or invert sugar have been intravenously administered to patients via a cannula inserted into the vena cava. While this technique provides a means by which the patient may intravenously receive high calorie solutions, it is not totally satisfactory in that insertion of the cannula is a surgical procedure not generally performed by a nurse, or many surgeons, and the dangerous possibility of septicemia or serious thrombosis in the vena cava, as well as potential damage of the heart and large vessels by the catheter tip.
U.S. Pat. No. 3,067,098 granted Dec. 4, 1962 to W. Pool and entitled "Intravenous Nourishment of Patients" discloses a high calorie solution that could be administered into a peripheral vein by virtue of a small amount of an anti-inflammatory steroid hormone such as hydrocortisone, cortisone, prednisolone, or prednisone included in the solution. The technique disclosed by Pool has not been widely practiced, however, because of the undesirable amounts of steriods that would be administered with prolonged usage.
U.S. Pat. No. 3,793,461 granted Feb. 19, 1974 to S. Yuen and entitled "Intravenous Administration of Maltose to Diabetics" discloses that glucose polymers of D.P.=2 (maltose) can be intravenously administered via a peripheral vein of a patient and that the maltose administered is utilized by human patients by a mechanism unknown to Yuen. The Yuen patent supports the findings of the present invention that glucose polymers can be utilized when intravenously administered into human patients. However, the use of maltose for intravenous therapy is somewhat limited by the fact that isotonic solutions of maltose supply only twice the calories of isotonic solutions of glucose and the relatively high cost of sufficiently pure maltose for intravenous administration.
U.S. Pat. No. 3,928,135 granted Dec. 23, 1975 to J. Milner and entitled "Process for the Production of Glucose Polymers" discloses that glucose polymer mixtures consisting of 3% glucose and glucose polymers of D.P. 2-10 can be administered intravenously. Milner further discloses an oral glucose polymer mixture which has a significant proportion of its molecules of a D.P. greater than 10.
An article by D. Bott, et al. at pp. 583-84 of The Pharmaceutical Journal of May 30, 1970 reported the consideration of a glucose polymer mixture, CALOREEN, for possible intravenous use. CALOREEN, which is an orally administered glucose polymer mixture, is reported to consist of 3% glucose, 7% maltose, 5% maltotriose and 85% polysaccharides having molecules of four to fifteen glucose units (A.D.P.=5) at p. 620 of an article by G. Berlynne, et al. entitled "A Soluble Glucose Polymer for Use in Renal Failure and Calorie Deprivation States".
Accordingly, it is clear that a nontoxic metabolizable high calorie solution that can be infused into a patient via a peripheral vein without causing venous thrombosis, thrombophlebitis, or other undesired side effects is needed.